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Biomedical subjects

M Di Giulio

Publications and source records attributed to M Di Giulio.

At least 37 records · Page 2Linked to original sources
PubMed1998

Artificial neural networks for the identification of the differences between "light" and "heavy" alcoholics, starting from five nonlinear biological variables.

This article makes a comparison among three types of evaluation systems based on a set of data composed of "heavy" alcoholics and "light" alcoholics. The three systems are: 1) a system based on genetic algorithms called BEAGLE; b) seven different types of Artificial Neural Networks; c) a metasystem called MetaNet. The technical aim was to compare the classification capability of these three systems in terms of two classes ("heavy" alcoholics and "light" alcoholics). From the results obtained, the MetaNet system stand out. Globally, it has the best result, followed by the two Artificial Neural Networks, Squash and Logicon Projection. The results obtained prove that the advanced elaboration data systems applied in the social and health fields can be employed in prevention programs having an aim to reduce the social impact of certain pathologies correlated with different kinds of dependence.

Alcoholism↗
PubMed1997

On the origin of the genetic code.

The main theories which have been suggested to explain the origin of genetic code organization are discussed. The coevolution theory, which considers the genetic code as a map of the biosynthetic relationships between amino acids, seems to be based on a mechanism that links it closely to certain stages of the origin of metabolism, which makes it preferable to other theories proposed as explanations of genetic code origin. Relationships, incompatibilities and compromises between the various theories are highlighted and these seem to indicate a certain lack of clarity in this field of research.

Animals↗
PubMed1997

On the RNA world: evidence in favor of an early ribonucleopeptide world.

A highly complex RNA world, as is sometimes presented in view of the widespread and diversified use of RNA enzymes, would have encountered many difficulties in passing to a world with catalysis mediated by proteins. These difficulties can be overcome by postulating a very early relationship between the nucleotide and the amino acid components. In particular, after asserting that some characteristics expressed by (nucleotide) coenzymes in catalysis are easier to understand if a close and early relationship between these coenzymes and amino acids is hypothesized, a model is presented for the origin of the enzyme-coenzyme complex. This model is essentially based on an intermediate formed by a tRNA-like molecule covalently linked to a polypeptide. The model attributes the majority of the catalytic role in the ribonucleoprotein world to the latter complex and thus it takes into account the birth of the key intermediate in the origin of protein synthesis-namely, peptidyl-tRNA, which would have otherwise been extremely difficult to select. The predictions of the model are discussed along with its robustness, using the data derived from the study of intermediary metabolism and those from molecular biology. Finally, the appearance of the genetic code in the late phase of the ribonucleopeptide world is discussed.

Animals↗
PubMed1997

Long-term results of percutaneous ethanol injection therapy for hepatocellular carcinoma in cirrhosis: a European experience.

The objective of our work was to evaluate the long-term results of percutaneous ethanol injection (PEI) for the treatment of hepatocellular carcinoma (HCC) in patients with liver cirrhosis. A total of 184 cirrhotic patients with HCC underwent PEI as the only anticancer treatment over an 8-year period. Patients were followed after therapy by means of clinical examinations, laboratory tests, and US and CT studies performed at regular time intervals. Survival rates were determined according to the Kaplan-Meier method. The overall survival was 67% at 3 years, 41% at 5 years, and 19% at 7 years. The 3-, 5-, and 7-year survival rates of patients with single HCC < or = 3 cm (78, 54, and 28%, respectively) were significantly higher (p < 0.01) than those of patients with single HCC of 3.1-5 cm (61, 32, and 16, respectively) or multiple HCCs (51, 21, and 0%, respectively). Survival of Child-Pugh A patients (79% at 3 years, 53% at 5 years, and 32% at 7 years) was significantly longer (p < 0.01) than that of Child-Pugh B patients (50% at 3 years, 28% at 5 years, and 8% at 7 years). A selected group of 70 patients with Child-Pugh A cirrhosis and single HCC < or = 3 cm had a 7-year survival of 42%. Long-term survival of cirrhotic patients with HCC treated with PEI is comparable to that reported in published series of matched patients submitted to surgical resection.

Adult↗
PubMed1996

The beta-sheets of proteins, the biosynthetic relationships between amino acids, and the origin of the genetic code.

Two forces are generally hypothesised as being responsible for conditioning the origin of the organization of the genetic code: the physicochemical properties of amino acids and their biosynthetic relationships (relationships between precursor and product amino acids). If we assume that the biosynthetic relationships between amino acids were fundamental in defining the genetic code, then it is reasonable to expect that the distribution of physicochemical properties among the amino acids in precursor-product relationships cannot be random but must, rather, be affected by some selective constraints imposed by the structure of primitive proteins. Analysis shows that measurements representing the 'size' of amino acids, e.g. bulkiness, are specifically associated to the pairs of amino acids in precurso-product relationships. However, the size of amino acids cannot have been selected per se but, rather, because it reflects the beta-sheets of proteins which are, therefore, identified as the main adaptive theme promoting the origin of genetic code organization. Whereas there are no traces of the alpha-helix in the genetic code table. The above considerations make it necessary to re-examine the relationship linking the hydrophilicity of the dinucleoside monophosphates of anticodons and the polarity and bulkiness of amino acids. It can be concluded that this relationship seems to be meaningful only between the hydrophilicity of anticodons and the polarity of amino acids. The latter relationship is supposed to have been operative on hairpin structures, ancestors of the tRNA molecule. Moreover, it is on these very structures that the biosynthetic links between precursor and product amino acids might have been achieved, and the interaction between the hydrophilicity of anticodons and the polarity of amino acids might have had a role in the concession of codons (anticodons) from precursors to products.

Amino Acids↗
PubMed1996

The origin of protein synthesis: on some molecular fossils identified through comparison of protein sequences.

Sequence data, even if only marginally significant, and evolutionary arguments suggest that a similarity may exist between class II aminoacyl-tRNA synthetases and proteins involved in the nonribosomal biosynthesis of peptide antibiotics, and more in general, those belonging to the family of adenylate-forming enzymes. If correct, this hypothesis of homology may imply that the first peptide syntheses might have occurred on phosphopantetheine molecules in a thioester world and/or on a variant of the coenzyme A (CoA) in an RNA world. Therefore, peptide synthesis probably evolved on tRNA-like molecules from the CoA (or a variant CoA molecule) that had the potential for nucleotide extension, that made possible the evolution to the current mechanism of protein synthesis. Our hypothesis on the existence of such homology implies that a series of evolutionary steps such as the existence of a primitive catalytic domain with poor substrate specificity towards both (amino acids + ATP + pre-CoA (and/or CoA)) and (amino acids + ATP + tRNA-like) molecules may have occurred. Therefore, the pre-CoA (and/or CoA) and the tRNA-like molecules were able to use this enzyme ambiguity for a certain period, thus giving weight to the scheme of evolutionary transitions mentioned above.

Amino Acid Sequence↗
PubMed1995

Was it an ancient gene codifying for a hairpin RNA that, by means of direct duplication, gave rise to the primitive tRNA molecule?

Some sequences of transfer RNAs (tRNAs) which are believed to possess many of the characteristics of the ancestral sequence of this molecule are constructed. Analysis of these ancestral sequences seems to indicate that: (i) self-alignment of these sequences makes it possible for the 3'-half of the reconstructed molecule to display a significant similarity to the 5'-half, thus indicating that the two halves of tRNA might be paralogous, and (ii) the 5'-half of the ancestral tRNA can reconstruct an almost perfect hairpin structure. These observations give weight to the hypothesis suggesting that the primitive tRNA molecule may have originated through direct duplication of an ancient gene codifying for a hairpin structure.

Base Sequence↗
PubMed1995

The phylogeny of tRNAs seems to confirm the predictions of the coevolution theory of the origin of the genetic code.

An extensive analysis of the evolutionary relationships existing between transfer RNAs, performed using parsimony algorithms, is presented. After building up an estimate of the tRNA ancestral sequences, these sequences are then compared using certain methods. The results seem to suggest that the coevolution hypothesis (Wong, J.T., 1975, Proc. Natl. Acad. Sci. USA 72, 1909-1912) that sees the genetic code as a map of the biosynthetic relationships between amino acids is further supported by these results, as compared to the hypotheses that see the physicochemical properties of amino acids as the main adaptative theme that led to the structuring of the genetic code.

Amino Acid Sequence↗
PubMed1994

On the origin of protein synthesis: a speculative model based on hairpin RNA structures.

A speculative model for the origin of protein synthesis based on aminoacylated hairpin RNAs is presented. The model shows how dimerization of these hairpin structures might have triggered the initial synthesis of oligopeptides. The evolution of these dimers seems to lead naturally both to the origin of the tRNA molecule and to the origin of protein synthesis. This co-evolution seems to be confirmed in the determinants of the tRNA identity that might represent the vestiges of the hypothesized model. Finally, the model lends itself to direct experimentation.

Animals↗
PubMed1994

The phylogeny of tRNA molecules and the origin of the genetic code.

The evolutionary relationships between transfer RNA (tRNA) molecules are analyzed by parsimony algorithms. The position of the topologies expected on the basis of the hypotheses made to explain the origin of the genetic code, on the frequency distribution of all the possible tree topologies of the evolutionary relationships between tRNAs seems to lead to the following conclusion: The hypothesis (Wong, J. T., Proc. Natl. Acad. Sci. USA, 1975, 72: 1909-1912) that sees the genetic code as a map of the biosynthetic relationships between amino acids seems to occupy a statistically significant position on these frequency distributions, thus reflecting a significant part of the tRNA phylogeny.

Base Sequence↗
PubMed1993

Origin of glutaminyl-tRNA synthetase: an example of palimpsest?

Sequence data and evolutionary arguments suggest that a similarity may exist between the C-terminal end of glutaminyl-tRNA synthetase (GlnRS) and the catalytic domain of glutamine amidotransferases (GATs). If true, this would seem to imply that the amidation reaction of the Glut-tRNA(Gln) complex was the evolutionary precursor of the direct tRNA(Gln) aminoacylation pathway. Since the C-terminal end of GlnRS does not now have an important functional role, it can be concluded that this sequence contains vestiges that lead us to believe that it represents a palimpsest. This sequence still conserves the remains of the evolutionary transition: amidation reaction-->aminoacylation reaction. This may be important in deciding which mechanism gave origin to the genetic code organization. These observations, together with results obtained by Gatti and Tzagoloff [J. Mol. Biol. (1991) 218:557-568], lead to the hypothesis that the class I aminoacyl-tRNA synthetases (ARSs) may be homologous to the GATs of the trpG subfamily, while the class II ARSs may be homologous to the GATs of the purF subfamily. Overall, this seems to point to the existence of an intimate evolutionary link between the proteins involved in the primitive metabolism and aminoacyl-tRNA synthetases.

Amino Acid Sequence↗
PubMed1992

On the origin of the transfer RNA molecule.

Data and arguments are given in favour of the hypothesis that the primitive tRNA molecule may have originated from a direct duplication event involving one of the two halves of the tRNA molecule. It seems that a molecule capable of assuming a hairpin structure was involved as a precursor in this duplication. The two halves of the present tRNAs could, therefore, be considered as paralogous.

Amino Acid Sequence↗
PubMed1992

The evolution of aminoacyl-tRNA synthetases, the biosynthetic pathways of amino acids and the genetic code.

In this paper the partition metric is used to compare binary trees deriving from (i) the study of the evolutionary relationships between aminoacyl-tRNA synthetases, (ii) the physicochemical properties of amino acids and (iii) the biosynthetic relationships between amino acids. If the tree defining the evolutionary relationships between aminoacyl-tRNA synthetases is assumed to be a manifestation of the mechanism that originated the organization of the genetic code, then the results appear to indicate the following: the hypothesis that regards the genetic code as a map of the biosynthetic relationships between amino acids seems to explain the organization of the genetic code, at least as plausibly as the hypotheses that consider the physicochemical properties of amino acids as the main adaptive theme that lead to the structuring of the code.

Amino Acids↗
PubMed1989

Some aspects of the organization and evolution of the genetic code.

In this paper, I define a measure of the relative position of each amino acid in the genetic code by means of a 21-dimensional vector describing its potential for mutation, in a single step, to each of the other amino acids, or to a chain termination codon. This measure allows us to make a systematic investigation of the type and number of the physicochemical properties of the amino acids that were involved in evolution. The polar character and size of amino acids are identified in this analysis as properties that played a leading role in the evolutionary history of the genetic code. The application of cluster analysis and discriminant analysis reveals the characteristics of the structural organization of the genetic code. Finally, I suggest the existence of a relationship between the molecular weight of the amino acids and the number of synonymous codons.

Amino Acids↗
PubMed1989

The extension reached by the minimization of the polarity distances during the evolution of the genetic code.

The level reached by the optimization of the polarity distances during the evolution of the genetic code was investigated. The results, although not conclusive, indicate that this optimization level is higher than the data reported in the literature. The results seem compatible with the reaching of an evolutionary minimum, with respect to the optimization of the polarity distances, by the genetic code during its formation.

Amino Acids↗